Site-specific radioisotope-labeled antibody using IgG-binding peptide

Abstract

The present invention relates to an IgG-binding peptide comprising a ligand capable of binding to a radioactive metal nuclide, an IgG-binding peptide labeled with a radioactive metal nuclide, a conjugate of the IgG-binding peptide and IgG, and a radionuclide imaging agent or a diagnostic agent for cancer comprising the IgG-binding peptide or the conjugate, etc.

The invention claimed is: 
     
       1. A peptide consisting of 13 to 17 amino acid residues represented by the following formula I:
   (X 1-3 )—C—(X 2 )—H-(Xaa1)-G-(Xaa2)-L-V—W—C—(X 1-3 )  (I) (SEQ ID NO: 38)
 
 wherein each X is independently any amino acid residue other than cysteine, 
 C is a cysteine residue, 
 H is a histidine residue, 
 Xaa1 is a lysine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, or diaminopropionic acid, 
 G is a glycine residue, 
 Xaa2 is a glutamic acid residue, a glutamine residue, or an asparagine residue, 
 L is a leucine residue, 
 V is a valine residue, and 
 W is a tryptophan residue, 
 wherein the peptide is capable of binding to human IgG, and wherein a ligand capable of binding to a radioactive metal nuclide is linked to the N terminus of the peptide, 
 G is a glycine residue, 
 Xaa2 is a glutamic acid residue, a glutamine residue, or an asparagine residue, 
 L is a leucine residue, 
 V is a valine residue, and 
 W is a tryptophan residue, 
 wherein the peptide is capable of binding to human IgG, and is labeled with a radioactive metal nuclide. 
 
     
     
       2. The peptide according to  claim 1 , wherein the radioactive metal nuclide is selected from the group consisting of  111 In,  89 Zr,  64 Cu,  67/68 Ga, and  99m Tc. 
     
     
       3. The peptide according to  claim 1 , wherein the ligand is a chelating agent. 
     
     
       4. The peptide according to  claim 3 , wherein the chelating agent is selected from the group consisting of diethylenetriaminepentaacetic acid (DTPA), deferoxamine, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and ethylenediaminetetraacetic acid (EDTA). 
     
     
       5. The peptide according to  claim 1 ,
 wherein the peptide consists of 13 to 17 amino acid residues represented by the following formula II:
   (X 1-3 )—C-(Xaa3)-(Xaa4)-H-(Xaa1)-G-(Xaa2)-L-V—W—C—(X 1-3 )  (II) (SEQ ID NO: 42)
 
 
 wherein each X is independently any amino acid residue other than cysteine, 
 C is a cysteine residue, 
 H is a histidine residue, 
 Xaa1 is a lysine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, or diaminopropionic acid, 
 G is a glycine residue, 
 Xaa2 is a glutamic acid residue, a glutamine residue, or an asparagine residue, 
 L is a leucine residue, 
 V is a valine residue, 
 W is a tryptophan residue, 
 Xaa3 is an alanine residue, a serine residue or a threonine residue, and 
 Xaa4 is a tyrosine residue or a tryptophan residue. 
 
     
     
       6. The peptide according to  claim 1 , wherein the peptide consists of 13 to 17 amino acid residues represented by the following formula I*:
   (Xbb1)-(Xbb2)-(Xbb3)-C—(X 2 )—H-(Xaa1)-G-(Xaa2)-L-V—W—C-(Xbb4)-(Xbb5)-(Xbb6)  (I*)
 
 C is a cysteine residue, 
 H is a histidine residue, 
 Xaa1 is a lysine residue, a cysteine residue, an aspartic acid residue, a glutamic acid residue, 2-aminosuberic acid, or diaminopropionic acid, 
 G is a glycine residue, 
 Xaa2 is a glutamic acid residue, a glutamine residue, or an asparagine residue, 
 L is a leucine residue, 
 V is a valine residue, 
 W is a tryptophan residue, 
 Xbb1 is S, G, F, R or none, 
 Xbb2 is D, G, A, S, P, homocysteine, or none, 
 Xbb3 is S, D, T, N, E or R, 
 Xbb4 is S, T or D, 
 Xbb5 is H, G, Y, T, N, D, F, homocysteine, or none, and 
 Xbb6 is Y, F, H, M or none. 
 
     
     
       7. The peptide according to  claim 1 , wherein the peptide consists of GPDCAYHKGELVWCTFH (SEQ ID NO: 37), wherein the two Cys (C) residues form an intramolecular SS bond.